Study of water channel aquaporin for treatment of perioperative heart failure

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10642
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: Nippon Medical School
• Principal Investigator: Amitani Ryosuke 日本医科大学, 医学部, 助教 (30763594)
• Co-Investigator(Kenkyū-buntansha): 藤井 正大 日本医科大学, 医学部, 准教授 (60297926) ; 別所 竜蔵 日本医科大学, 医学部, 准教授 (60281432)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: アクアポリン２ / アクアポリン７ / 心筋保護 / 周術期管理

Outline of Final Research Achievements

We examined changes in plasma AVP and urinary AQP2 during perioperative period (before operation, on the first, fourth and seventh postoperative day) in patients who underwent cardiac surgery using cardiopulmonary bypass. The plasma AVP showed a transient increase significantly on the first postoperative day, and turned to decrease on the fourth postoperative day. Urinary AQP2 excretion showed similar changes. In patients undergoing off-pump coronary artery bypass grafting, postoperative plasma AVP and urinary AQP2 levels were elevated similar to those with cardiopulmonary bypass. AQP7, a member of the aquaglyceroporin family that is permeated by glycerol and water, has been observed in cardiac tissue. We have investigated a protective efficacy of STH2 in an experimental preparation of isolated AQP7 knock-out murine hearts. We demonstrated the myocardial protection afforded by STH2 even through AQP7 was absent.

Free Research Field

心臓血管外科

Academic Significance and Societal Importance of the Research Achievements

血漿バソプレッシンは体液量と血漿浸透圧の調節を行っているが，心不全患者では腎集合管へ作用し水チャンネルであるアクアポリン2を介して体液貯留・浮腫の一因となる．心臓血管外科領域においても術中侵襲により血漿バソプレッシンが上昇することは知られてきたが，本研究により血漿バソプレッシン増加に相関して尿中アクアポリン2排泄の増加がみられ，術後患者でもこのメカニズムが維持されていることが判明した．また，肥満患者ではアクアポリン7チャンネルが欠損していることが示唆されているが，マウスを用いた基礎実験により心筋のアクアポリン7欠損状態でもSt Thomas2号液による心筋保護効果は発揮されることが証明された．